5-Amino-1MQ 50mg

What is 5-Amino-1MQ ?

5-Amino-1MQ (5-amino-1-methylquinolinium iodide) is a small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT), not a peptide. It is supplied as a lyophilised powder in 10mg and 50mg vials.

The active species is the quaternary cation C₁₀H₁₁N₂⁺ (159.21 g/mol), supplied as the iodide salt. Its target, NNMT, is a cytosolic enzyme that methylates nicotinamide to 1-methylnicotinamide using S-adenosyl-L-methionine (SAM). 5-Amino-1MQ binds the nicotinamide substrate site. Neelakantan et al. (J Med Chem, 2017) screened several N-methylated scaffolds and found quinoliniums the most promising, with IC₅₀ values around 1 µM. The reported IC₅₀ for 5-Amino-1MQ is 1.2 µM.

5-Amino-1MQ Research Applications

• Enzyme assays : NNMT inhibition measured by 1-methylnicotinamide formation or S-adenosylhomocysteine release.
• Cell target engagement : in differentiated 3T3-L1 adipocytes, 5-Amino-1MQ lowered intracellular 1-methylnicotinamide with an EC₅₀ of about 2.3 µM (Neelakantan et al., 2018).
• Selectivity panels : no inhibition of DNMT1, and no calculable IC₅₀ against PRMT3 or COMT (Neelakantan et al., 2018).
• Rodent metabolism : in-vivo NNMT work in adipose tissue and liver follows antisense Nnmt knockdown in mice (Kraus et al., Nature, 2014).

Because it competes at the nicotinamide site, not the SAM cofactor site, 5-Amino-1MQ is also the substrate-competitive reference against which bisubstrate and covalent NNMT inhibitors are benchmarked.

5-Amino-1MQ vs NAD+ Precursors (NAD+, NMN, NR)

The two approach the same pathway from opposite ends. NAD+, NMN and nicotinamide riboside add material to the NAD+ salvage route. 5-Amino-1MQ removes a drain on it. By blocking NNMT, it stops nicotinamide being methylated to 1-methylnicotinamide and spares the SAM that reaction would spend. In cultured adipocytes, NNMT inhibitors lowered intracellular 1-methylnicotinamide and raised NAD+ and SAM (Neelakantan et al., Biochem Pharmacol, 2018). 5-Amino-1MQ did not inhibit NAMPT, an NAD+ salvage enzyme, at up to 100 µM.

The evidence differs too. The precursor literature includes human pharmacokinetic work, while every in-vivo 5-Amino-1MQ study is in rodents.

Research Overview

5-Amino-1MQ is a small molecule, not a peptide, and getting that right is the first step in reading the literature: searches for 5 amino 1mq peptide return a compound that is chemically a quaternary quinolinium salt. Its full name is 5-amino-1-methylquinolinium. The active species is the cation C₁₀H₁₁N₂⁺ at 159.21 g/mol, and it is supplied as the iodide salt, C₁₀H₁₁IN₂, molecular weight 286.11 g/mol, CAS 42464-96-0. Its molecular target is nicotinamide N-methyltransferase (NNMT), a cytosolic S-adenosyl-L-methionine-dependent methyltransferase that converts nicotinamide to 1-methylnicotinamide, consuming SAM and releasing S-adenosylhomocysteine. Because nicotinamide would otherwise re-enter the NAD+ salvage pathway through NAMPT and NMN, NNMT activity sits at a junction between cellular methylation capacity and NAD+ regeneration, which is why the enzyme became a target after Kraus and colleagues (Nature, 2014) reported the consequences of antisense Nnmt knockdown in white adipose tissue and liver. 5-Amino-1MQ is a substrate-mimetic inhibitor that occupies the nicotinamide binding site, with a reported IC₅₀ of 1.2 ± 0.1 μM (Neelakantan et al., J Med Chem, 2017). Its practical advantage over earlier quinolinium analogues is permeability. Neelakantan and colleagues (Biochem Pharmacol, 2018) reported that 1-methylquinolinium and 1-methylnicotinamide showed no measurable passive diffusion in their assays, whereas 5-amino-1MQ crossed by both passive and active routes with no detectable efflux in Caco-2 cells, and lowered intracellular 1-methylnicotinamide in differentiated 3T3-L1 adipocytes with an EC₅₀ near 2.3 μM. Selectivity was reported against COMT and against the SAM-dependent DNA and protein methyltransferases DNMT1 and PRMT3. Human evidence is absent: every in-vivo study published to date is rodent, and no NNMT inhibitor is approved anywhere. Supplied for in-vitro research use only.

Storage and Reconstitution

Store the dry powder sealed at -20°C, away from light and moisture. Keep solutions at 2-8°C in amber or foil-wrapped vessels and freeze single-use aliquots for longer storage. Iodide salts are light-sensitive, so re-check identity if a stored solid or solution turns yellow.

Vials are sold on their own, without bacteriostatic water for mixing or other supplies.

How to reconstitute and handle

5-Amino-1MQ is a salt, not a peptide, so gentle handling is for sterility only. Let the vial reach room temperature, add bacteriostatic water or your assay buffer, and swirl or invert until fully dissolved. As a permanently charged cation it needs no organic cosolvent for aqueous work, though DMSO stocks are common in cell screens. Label the solution with its concentration and state whether it refers to the iodide salt (286.11 g/mol) or the free cation (159.21 g/mol).

• Store the dry solid at -20°C, sealed and protected from light and moisture. Allow the vial to reach room temperature before opening so condensation does not settle on the contents.
• Because this is a small-molecule salt rather than a peptide, the usual peptide precautions about mechanical shear and methionine or tryptophan oxidation do not apply. It can be dissolved by gentle inversion; there is no need to avoid agitation for structural reasons.
• Dissolve in bacteriostatic water or the aqueous buffer required by the assay. As a permanently charged quaternary cation it is water-soluble and does not require organic cosolvent for aqueous work, though DMSO stocks are common in cell-based screens.
• Protect solutions from light and store at 2-8°C, preparing single-use aliquots for longer storage at -20°C. Iodide salts are light-sensitive and darkening or discolouration of a stored solid or solution warrants re-checking identity before use.
• For NNMT assays remember that the compound competes at the nicotinamide substrate site, so the apparent potency depends on the nicotinamide concentration used. Report substrate and SAM concentrations alongside any IC₅₀ so results can be compared with the published values.
• Handle under standard laboratory chemical hygiene. This is a research chemical supplied for in-vitro use only and is not for human or veterinary administration.

For the full method, see the peptide reconstitution guide and the reconstitution calculator.

Research References

• Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase (Neelakantan et al., J Med Chem, 2017)
• Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase (Neelakantan et al., Biochem Pharmacol, 2018)
• Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity (Kraus et al., Nature, 2014)

Published research on 5-Amino-1MQ is indexed on PubMed. See our full UK buyer's guide for 5-Amino-1MQ and UK buyer's guide for 5-Amino-1MQ 50mg.